The synthesis and release of prostaglandin-like materials by tissues have been observed during pathophysiologic conditions such as tissue hypoxia, regional ischemia, and circulatory shock. Little is known about the cellular factors which initiate this enhanced postanoid production. It has been assumed that both the mechanism initiating the synthesis and the pattern of prostaglandin formation from archidonic acid during the pathophysiologic conditions are identical to those present in non-injured tissue. The proposed studies seek to test these assumptions in an isolated, rabbit liver preparation. The project will be carried out in three phases. The first phase will attempt to establish whether a common mechanism exists by which different types of injurious stimuli are able to initiate prostanoid biosynthesis. The second phase of the study will determine whether phospholipase A2 and calcium are required factors in the injury related initiation of prostanoid formation as they are in normal tissue, or whether prostanoids are formed as a consequence of loss of cellular structural integrity under adverse conditions. The final phase will involve assessing the patterns and magnitude of radiolabeled arachidonic acid metabolism in normal and injured tissues in an attempt to determine whether the injury process can influence which specific types of prostaglandin-like materials are formed. Data from these proposed studies will provide basic information relating to the mechanisms involved in the enhanced activity of the arachidonic acid cascade during periods of tissue injury. They will also provide information relating to the factors controlling the component pathways of the cascade. This information will lead to a better understanding of the role which endogenously synthetized prostanoids may play in cellular homeostasis and will aid in the future design of therapeutic approaches to the clinical management of cellular injury, death, and the salvage of injured tissue.